For millennia, humankind has relied on plant derivatives for the prevention and treatment of a wide variety of aliments. For example, in China, various teas have been used as a crude medicine for over 4,000 years. And more recently, there has been considerable interest in taking advantage of various plant extracts as a source of health promoting substances such as, natural oxidants, flavonoids, and phenolic compounds. In part, this trend is due to a growing body of evidence demonstrating that some of these compounds have beneficial properties that may be advantageous in preventing or delaying, for example, the onset of cardiovascular disease.
Indeed, several studies have suggested that beneficial fatty acid and other plant derived compounds have desirable effects ranging from reducing lipid levels, lowering blood pressure, and regulating inflammatory disease. For example, barley has been shown to be particularly effective in lowering lipid levels in test animals (Quereshi et al., Lipids, 20:817-24 (1985)). And in particular, a tocochromanol isolated from barley extract has been identified as an active compound suitable for treating hypercholesterolemia (Quereshi et al., J. Biol. Chem., 261:10544-50 (1986)). Similarly, other tocochromanols, for example, γ-tocotrienol and δ-tocotrienol have also been shown to reduce hypercholesterolemia in mammals (European patent application 421,419).
In general, hypercholesterolemia involves high serum cholesterol levels that are associated with a number of diseases including atherosclerosis, arteriosclerosis, and cardiovascular disease. In addition, high serum cholesterol levels are also seen in patients suffering from other diseases such as diabetes mellitus and familial hypercholesterolemia. While improvement of lipoprotein profiles and a decrease in total serum and low density lipoprotein cholesterol have been shown to slow the progression of such diseases, the exact link between hypercholesterolemia and, most notably, cardiovascular disease, has remained obscure. As a result, cardiovascular disease continues to remain a leading cause of death in the United States.
In part, the reason a cure for cardiovascular disease has remained elusive, is that the etiology of the disease may be the result of series of complex interactions involving genetic factors, lipoprotein metabolism, clotting functions, and even lifestyle choices (e.g., diet, exercise). Interestingly, populations consuming large amounts of cereal grains have a lower incidence of cardiovascular disease and lower cholesterol levels. Studies looking at the beneficial properties of cereal diets have attributed these effects to naturally occurring tocochromanols, and these compounds have been found in a wide variety of plant sources (Quereshi et al., Am. J. Clin. Nutr., 53:1021S-6S (1991)).
As a class of compounds, tocochromanols include the tocopherols and the tocotrienols. Tocopherols, including δ-α-tocopherol are essentially the active ingredient in vitamin E and have been extensively studied. A number of beneficial properties have been attributed to the tocopherols such as reduced platelet aggregation and antioxidant functions (Niki et al., Annals of the New York Academy of Sciences, 570:23-31 (1989); Fukuzawa et al., Annals of the New York Academy of Sciences, 570:449-453 (1989)).
The tocotrienols have been less well studied although recent evidence suggests that these compounds may also be biologically active (see for example U.S. Pat. Nos. 5,591,772 and 4,603,142). Naturally occurring tocotrienols including α- β-, γ-, and δ-tocotrienol have been identified in and isolated from a variety of sources including, e.g. rice, rice bran, barley, coconut, and palm. These compounds exhibit varying degrees of hypercholesterolemic activity and have also been used as antithrombotic agents and antioxidants.
Additional sources of tocopherols, tocotrienols, and other therapeutically beneficial compounds which can be used safely and effectively, for example, as a hypercholesterolemic, antithrombotic, antioxidizing, antiatherogenic, antiinflammatory, and immunoregulatory agents, would be of great benefit.